Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain.

Neuromelanin-sensitive MRI (NM-MRI) purports to detect the content of neuromelanin (NM), a product of dopamine metabolism that accumulates with age in dopamine neurons of the substantia nigra (SN). Interindividual variability in dopamine function may result in varying levels of NM accumulation in the SN; however, the ability of NM-MRI to measure dopamine function in nonneurodegenerative conditions has not been established. Here, we validated that NM-MRI signal intensity in postmortem midbrain specimens correlated with regional NM concentration even in the absence of neurodegeneration, a prerequisite for its use as a proxy for dopamine function. We then validated a voxelwise NM-MRI approach with sufficient anatomical sensitivity to resolve SN subregions. Using this approach and a multimodal dataset of molecular PET and fMRI data, we further showed the NM-MRI signal was related to both dopamine release in the dorsal striatum and resting blood flow within the SN. These results suggest that NM-MRI signal in the SN is a proxy for function of dopamine neurons in the nigrostriatal pathway. As a proof of concept for its clinical utility, we show that the NM-MRI signal correlated to severity of psychosis in schizophrenia and individuals at risk for schizophrenia, consistent with the well-established dysfunction of the nigrostriatal pathway in psychosis. Our results indicate that noninvasive NM-MRI is a promising tool that could have diverse research and clinical applications to investigate in vivo the role of dopamine in neuropsychiatric illness.

A distinct inferential mechanism for delusions in schizophrenia.

Delusions, a core symptom of psychosis, are false beliefs that are rigidly held with strong conviction despite contradictory evidence. Alterations in inferential processes have long been proposed to underlie delusional pathology, but previous attempts to show this have failed to yield compelling evidence for a specific relationship between inferential abnormalities and delusional severity in schizophrenia. Using a novel, incentivized information-sampling task (a modified version of the beads task), alongside well-characterized decision-making tasks, we sought a mechanistic understanding of delusions in a sample of medicated and unmedicated patients with schizophrenia who exhibited a wide range of delusion severity. In this novel task, participants chose whether to draw beads from one of two hidden jars or to guess the identity of the hidden jar, in order to minimize financial loss from a monetary endowment, and concurrently reported their probability estimates for the hidden jar. We found that patients with higher delusion severity exhibited increased information seeking (i.e. increased draws-to-decision behaviour). This increase was highly specific to delusion severity as compared to the severity of other psychotic symptoms, working-memory capacity, and other clinical and socio-demographic characteristics. Delusion-related increases in information seeking were present in unmedicated patients, indicating that they were unlikely due to antipsychotic medication. In addition, after adjusting for delusion severity, patients as a whole exhibited decreased information seeking relative to healthy individuals, a decrease that correlated with lower socioeconomic status. Computational analyses of reported probability estimates further showed that more delusional patients exhibited abnormal belief updating characterized by stronger reliance on prior beliefs formed early in the inferential process, a feature that correlated with increased information seeking in patients. Other decision-making parameters that could have theoretically explained the delusion effects, such as those related to subjective valuation, were uncorrelated with both delusional severity and information seeking among the patients. In turn, we found some preliminary evidence that subjective valuation (rather than belief updating) may explain group differences in information seeking unrelated to delusions. Together, these results suggest that abnormalities in belief updating, characterized by stronger reliance on prior beliefs formed by incorporating information presented earlier in the inferential process, may be a core computational mechanism of delusional ideation in psychosis. Our results thus provide direct empirical support for an inferential mechanism that naturally captures the characteristic rigidity associated with delusional beliefs.

Does Surgical Day of the Week Affect Hospital Course and Outcomes for Patients Undergoing Adult Spinal Deformity Surgery?

STUDY DESIGN: Retrospective Cohort Analysis. OBJECTIVES: Extended hospital length of stay (LOS) poses a significant cost burden to patients undergoing adult spinal deformity (ASD) surgery. The purpose of this study is to investigate the relationship between late-week surgery and LOS in patients undergoing ASD surgery. METHODS: 256 patients who underwent ASD surgery between January 2018 and December 2021 by a single fellowship-trained orthopedic spine surgeon comprised the patient sample. Demographics, intraoperative, and perioperative data were collected for the 256 patients who underwent ASD surgery. Patients were divided into two groups based on surgical day of the week: (1) Early-week (Monday/Tuesday) n = 126 and (2) Late-week (Thursday/Friday) n = 130. Descriptive statistics, T-tests, and linear and logistic regression models were used to analyze the data. RESULTS: Surgical details and sociodemographic characteristics did not differ between the groups. When controlling for TLIF/DLIF status and PSO status there was no difference in mean length of stay between the groups. The late-week group was associated with a greater risk of 30-day readmission, but there was no difference in complications, infections, or intraoperative complications. CONCLUSIONS: We found no difference in mean length of stay between surgeries performed early in the week vs late in the week. Although late-week surgeries had higher 30-day readmission risk, all other outcomes, including complication rates, showed no significant differences. When adequate weekend post-operative care is available, we do not advise restricting ASD surgeries to specific weekdays.

Predicting Complications in 153 Lumbar Pedicle Subtraction Osteotomies by a Single Surgeon Over a 6-Year Period.

INTRODUCTION: Pedicle subtraction osteotomy (PSO) is a complex surgical procedure that provides correction of moderate sagittal imbalance. Surgical complications have adverse effects on patient outcomes and healthcare costs, making it imperative for clinical researchers to focus on minimizing complications. However, when it comes to risk modeling of PSO surgery, there is currently no consensus on which patient characteristics or measures should be used. This study aimed to describe complications and compare the performance of various sociodemographic characteristics, surgical variables, and established risk indices in predicting postoperative complications, infections, and readmissions after lumbar PSO surgeries. METHODS: A review was conducted on 191 patients who underwent PSO surgery at a single institution by a single fellowship-trained orthopaedic spine surgeon between January 1, 2018, and December 31, 2021. Demographic, intraoperative, and postoperative data within 30 days, 1 year, and 2 years of the index procedure were evaluated. Descriptive statistics, t-test, chi-squared analysis, and logistic regression models were used. RESULTS: Intraoperative complications were significantly associated with coronary artery disease (odds ratios [OR] 3.95, P = 0.03) and operating room time (OR 1.01, P = 0.006). 30-day complications were significantly cardiovascular disease (OR 2.68, P = 0.04) and levels fused (OR 1.10, P = 0.04). 2-year complications were significantly associated with cardiovascular disease (OR 2.85, P = 0.02). 30-day readmissions were significantly associated with sex (4.47, 0.04) and length of hospital stay (χ2 = 0.07, P = 0.04). 2-year readmissions were significantly associated with age (χ2 = 0.50, P = 0.03), hypertension (χ2 = 4.64, P = 0.03), revision surgeries (χ2 = 5.46, P = 0.02), and length of hospital stay (χ2 = 0.07, P = 0.03). DISCUSSION: This study found that patients with coronary vascular disease and longer fusions were at higher risk of postoperative complications and patients with notable intraoperative blood loss were at higher risk of postoperative infections. In addition, physicians should closely follow patients with extended postoperative hospital stays, with advanced age, and undergoing revision surgery because these patients were more likely to be readmitted to the hospital.

Generalizability and Out-of-Sample Predictive Ability of Associations Between Neuromelanin-Sensitive Magnetic Resonance Imaging and Psychosis in Antipsychotic-Free Individuals.

Importance: The link between psychosis and dopaminergic dysfunction is established, but no generalizable biomarkers with clear potential for clinical adoption exist. Objective: To replicate previous findings relating neuromelanin-sensitive magnetic resonance imaging (NM-MRI), a proxy measure of dopamine function, to psychosis severity in antipsychotic-free individuals in the psychosis spectrum and to evaluate the out-of-sample predictive ability of NM-MRI for psychosis severity. Design, Setting, and Participants: This cross-sectional study recruited participants from 2019 to 2023 in the New York City area (main samples) and Mexico City area (external validation sample). The main samples consisted of 42 antipsychotic-free patients with schizophrenia, 53 antipsychotic-free individuals at clinical high risk for psychosis (CHR), and 52 matched healthy controls. An external validation sample consisted of 16 antipsychotic-naive patients with schizophrenia. Main Outcomes and Measures: NM-MRI contrast within a subregion of the substantia nigra previously linked to psychosis severity (a priori psychosis region of interest [ROI]) and psychosis severity measured using the Positive and Negative Syndrome Scale (PANSS) in schizophrenia and the Structured Interview for Psychosis-Risk Syndromes (SIPS) in CHR. The cross-validated performance of linear support vector regression to predict psychosis severity across schizophrenia and CHR was assessed, and a final trained model was tested on the external validation sample. Results: Of the 163 included participants, 76 (46.6%) were female, and the mean (SD) age was 29.2 (10.4) years. In the schizophrenia sample, higher PANSS positive total scores correlated with higher mean NM-MRI contrast in the psychosis ROI (t37 = 2.24, P = .03; partial r = 0.35; 95% CI, 0.05 to 0.55). In the CHR sample, no significant association was found between higher SIPS positive total score and NM-MRI contrast in the psychosis ROI (t48 = -0.55, P = .68; partial r = -0.08; 95% CI, -0.36 to 0.23). The 10-fold cross-validated prediction accuracy of psychosis severity was above chance in held-out test data (mean r = 0.305, P = .01; mean root-mean-square error [RMSE] = 1.001, P = .005). External validation prediction accuracy was also above chance (r = 0.422, P = .046; RMSE = 0.882, P = .047). Conclusions and Relevance: This study provided a direct ROI-based replication of the in-sample association between NM-MRI contrast and psychosis severity in antipsychotic-free patients with schizophrenia. In turn, it failed to replicate such association in CHR individuals. Most critically, cross-validated machine-learning analyses provided a proof-of-concept demonstration that NM-MRI patterns can be used to predict psychosis severity in new data, suggesting potential for developing clinically useful tools.

Differences in Financial Conflicts of Interest Among Participants in a National Spine Conference.

STUDY: Retrospective Study. OBJECTIVE: At the North American Spine Society (NASS) conference, participants may influence spine surgery practices and patient care through their contributions. Therefore, their financial conflicts of interest are of notable interest. This study aims to compare the demographics and payments made to participating surgeons. METHODS: A list of 151 spine surgeons was created based on those who participated in the 2022 NASS conference. Demographic information was obtained from public physician profiles. General payments, research payments, associated research funding, and ownership interest were collected for each physician. Descriptive statistics and two-tailed t-tests were used. RESULTS: In 2021, 151 spine surgeon participants received industry payments, totaling USD 48 294 115. The top 10% of orthopedic surgeons receiving payments accounted for 58.7% of total orthopedic general value, while the top 10% of neurosurgeons accounted for 70.1%. There was no significant difference between these groups' general payment amounts. Surgeons with 21-30 years of experience received the most general funding. There was no difference in funding between surgeons in academic or private settings. For all surgeons, royalties accounted for the largest percentage of the general value exchanged, while food/beverage accounted for the largest percentage of transactions. CONCLUSIONS: Our study found that only years of experience had a positive association with general payments, and most monetary value belonged to a small handful of surgeons. These participants receiving significant money may promote techniques requiring products of companies providing their compensation. Future conferences may require disclosure policy changes so attendees understand the degree of funding participants receive.

Rethinking delusions: A selective review of delusion research through a computational lens.

Delusions are rigid beliefs held with high certainty despite contradictory evidence. Notwithstanding decades of research, we still have a limited understanding of the computational and neurobiological alterations giving rise to delusions. In this review, we highlight a selection of recent work in computational psychiatry aimed at developing quantitative models of inference and its alterations, with the goal of providing an explanatory account for the form of delusional beliefs in psychosis. First, we assess and evaluate the experimental paradigms most often used to study inferential alterations in delusions. Based on our review of the literature and theoretical considerations, we contend that classic draws-to-decision paradigms are not well-suited to isolate inferential processes, further arguing that the commonly cited 'jumping-to-conclusion' bias may reflect neither delusion-specific nor inferential alterations. Second, we discuss several enhancements to standard paradigms that show promise in more effectively isolating inferential processes and delusion-related alterations therein. We further draw on our recent work to build an argument for a specific failure mode for delusions consisting of prior overweighting in high-level causal inferences about partially observable hidden states. Finally, we assess plausible neurobiological implementations for this candidate failure mode of delusional beliefs and outline promising future directions in this area.